Flavourant compounds

ABSTRACT

Use as a flavour ingredient of an aliphatic or aromatic unsaturated amide of formula (I).

This invention relates to flavourant molecules for use in foods andbeverages.

New and interesting flavour ingredients are always being sought. To beof any practical use for flavourists, ingredients are needed that notonly possess interesting organoleptic properties, but they should alsobe inexpensive to produce and stable during long periods of storage andto processing conditions that may comprise elevated temperatures andhumidity, and extremes of pH.

Highly flavoured and pungent compounds are particularly valued insouthern Asian cuisine. Typical of these are certain sanshoolderivatives. However, a problem with the known sanshool derivatives isthat they are unstable; they tend to polymerise easily and are thereforedifficult to store over prolonged periods and are difficult toincorporate in processed consumables that create conditions promotinginstability.

Thus, the prior art goes no further than to make certain empiricalobservations concerning the organoleptic properties of these compounds.It does not give any hint or suggestion as to problems with instability,and so naturally does not teach solutions for overcoming instability.Further, the art does not provide any technical teaching as to theinfluence of the compounds' structure on their organoleptic properties.

It has now been found that certain aliphatic and aromatic unsaturatedamides are easily synthesised, are relatively stable during manufactureand under storage and processing conditions commonly experienced in themanufacture of consumables, and possess interesting pungent odours andleave a pleasing tingling sensation in the mouth. Therefore, theinvention provides in a first aspect the use as a flavour ingredient ofat least one compound according to the formula (I)

wherein,

-   R′ is H, or OH, and n is 1 or 2, R″ being selected such that-   (a) when n=2, R″ is a group of the formula    wherein m is 1, 2 or 3;-   R′″ and R′″ are independently selected from H, C1-C4 alkyl, benzyl,    or-   R′″ and R′″ together with the carbon atom to which they are attached    form a 5- or 6-membered carbocyclic ring,-   R^(V) is alkyl or alkenyl or a substituted alkyl or unsubstituted    alkenyl that does not contain any aliphatic conjugated double bonds,    and is preferably a linear or branched alkyl group having from 1 to    6 carbon atoms, or a linear or branched alkenyl group having 2 to 6    carbon atoms;    or-   (b) when n=1, R″ is selected from a group as described under (a) and    a phenyl group.

Use of these compounds as flavouring compounds gives to food a pungentnote and imparts a pleasant tingling sensation in the mouth. Theinvention therefore also provides a method for imparting a pungentflavour to a food product, comprising the addition to the food productof a compound of the type hereinabove described.

The compounds hereinabove described are not prone to polymerisation. Thecompounds share common functional features that may be characterised byone or two double bonds in the trans configuration adjacent the carbonylgroup, and a further double bond, provided in the group R″ that is inthe cis-configuration. This trans-cis, or trans-trans-cis configurationis important to preserve the pungent flavour note. Furthermore, thegroup Rv can tolerate additional unsaturation but it must not containany conjugated unsaturation, unless the conjugated unsaturation ispresent in an aromatic motif such as a phenyl group. It is believed thataliphatic conjugated saturation in this part of the molecule results ininstability and a tendency for the molecules to polymerise. Incontradistinction to the prior compounds mentioned above, none of thecompounds of formula (I) contain such functionality. This functionalityis essential for achieving these desirous properties, and is entirelyunpredictable having regard to the prior art.

Some of the abovementioned compounds are novel. Therefore, the inventionalso provides a compound of the formula

wherein the moieties therein are selected according to the followingtable: Compound R′ R″ R″′ R″″ n 1 H B Methyl Methyl 2 2 OH C MethylMethyl 2wherein B and C are each a group of the formula

wherein in B R^(v) is an ethyl radical; and in C R^(v) is a methylradical.

Compounds for use in the present invention may be prepared according tosynthetic procedures known in the art from readily available startingmaterials.

Aliphatic unsaturated amides of formula (I) may be prepared in a one-potsynthesis, coupling diethyl N-substituted phosphonoacetamide and anappropriately substituted aldehyde using butyl lithium in a suitable drysolvent such as THF according to classic Wittig-Horner-Emmons chemistry.The N-substituted phosphonoacetamide may be N-isobutylphosphonoacetamide and the aldehyde may be nonadienal, although theskilled person will understand that other starting aldehydes that arecommonly available or can be made according to known syntheses fromavailable starting materials, may be employed to provide compounds ofthe present invention.

Aromatic unsaturated amides according to formula (I) are likewise formedby a simple synthetic protocol, using an appropriately substituted amineand cinnamic acid or an appropriately substituted cinnamic acid, or inthe case of n=2 the 5-phenyl-penta-2,4dienoic acid, or substituted5-phenyl-penta-2,4dienoic acid. Further details relating to thesynthesis of the compounds of formula (I) are disclosed in the Examplesset forth in detail below.

A compound for use in the present invention imparts a pungent, spicynote to consumables. It also leaves a pleasant tingling sensation in themouth without any attendant burning or pain sensation. A compound of thepresent invention or a mixture thereof may be used as a flavouringredient in flavour compositions. A compound or mixture of compoundsmay be blended with other flavour ingredients in said compositions. Acompound or mixture of compounds imparts a particularly interesting noteto all kinds of savoury food products and also to beverages, and is alsointeresting in enhancing the performance of coolant compounds orcompositions.

In addition to their combination with other flavour ingredients, flavourcompositions may contain additional excipients that are commonlyemployed in the art for improving or enhancing the performance of foodor beverage products, for example preservatives, colourants, emulsifiersand encapsulating materials and formulations.

Flavour compositions as herein above described may be added to processedconsumables during their processing, or they may actually be consumablesin their own right, e.g. condiments such as sauces and the like.

The flavourant qualities of compounds of the formula (I) may be evidentover a broad range of concentrations. For example, in the case of a foodproduct such as soups, condiments and the like, a compound or mixture ofcompounds may be present in amounts ranging from 0.01 to 1.0% by weight,whereas, in the case of a beverage, such as alcoholic or soft drinks, acompound or a mixture thereof may be present in a concentration rangingfrom 0.0001 to 500 mg/kg.

Whereas the compounds of formula (I) are described as flavourantingredients, their unusual property of providing a tingling sensation,and their organoleptic properties may be usefully employed in personalcare products or cosmetics, that are to be topically applied whereuponthey may impart a fresh tingling sensations. In such compositions, theymay be applied in amounts ranging from 0.01 to 10% by weight, morepreferably 0.1 to 1% by weight.

There now follows a series of nonlimiting examples that serve toillustrate the invention.

EXAMPLE 1 N-isobutyl E2, E4, Z8-undecatrienamide (Compound 1 in theTable above)

In a procedure based on a published method (Tetrahedron Lett. 1985, 26(20), 2477-2480), at 0° C., in a round-bottom flask under an inertatmosphere of nitrogen, a solution of 2.77 g (11 mmol) of diethylN-isobutyl phosphonoacetamide in 20 mL of dry tetrahydrofuran is addedto 15.5 mL of a 1.5M solution of butyl lithium (23 mmol) in hexane. Themixture is stirred at 0° C. for thirty minutes. A solution of 1.4 g ofE2,Z6-nonadienal in 5 mL of dry tetrahydrofuran is then added dropwiseto the stirred reaction mixture. The mixture is stirred at 0° C. for twohours. The reaction mixture is then diluted in 100 mL of hexane andwashed with a saturated aqueous solution of ammonium chloride. Theorganic phase is collected and dried over anhydrous magnesium sulfate,filtered and concentrated. The residue is purified by chromatography onsilica gel to give 0.5 g of product as a white fluffy powder.

1H NMR (δ in ppm): 7.2 (doublet of doublet), 6.1 (multiplet), 5.75(doublet), 5.34 (multiplet), 3.2 (triplet), 2.2 (multiplet), 2.0(quintuplet), 1.8 (septuplet), 0.96 (triplet), 0.93 (doublet).

EXAMPLE 2 Preparation of 3-phenyl-acryloyl chloride

In a round-bottom flask under an inert atmosphere of nitrogen, a mixtureof 37.04 g (0.25 mol) of cinnamic acid, 44.6 g [0.375 mol] of thionylchloride and 2 drops of pyridine were heated at reflux for 4 h. The redmixture was concentrated (40° C./125 mbar) and 42.7 g of a brownish oilwere recovered.

Preparation of 3-phenyl-N-butyl-acrylamide

In a round-bottom flask under an inert atmosphere of nitrogen, a mixtureof 4.1 g [25 mmol] of 3-phenyl-acryloyl chloride, 25 ml of drytetrahydrofuran, 5 ml of pyridine was added. 1.77 g [30 mmol] ofiso-butylamine was added over a period of 30 min at room temperature.The mixture was stirred for 5 h at room temperature. The reactionmixture was diluted with methyl t-butyl ether and extracted with water.The organic phase was washed with aqueous hydrochloric acid (1N) andbrine, dried over anhydrous magnesium sulfate, filtered andconcentrated. The residue was crystallized from MTBE/hexane to give 4.1g of product as a yellowish fluffy powder.

¹H NMR (δ in ppm): 7.6 (doublet, 1H), 7.5 (multiplet, 2H), 7.4(multiplet, 3H), 6.4 (doublet, 1H), 5.8 (singlet, broad, 1H), 3.4(quartet, 2H), 1.6 (sixtuplet, 2H), 1.0 (triplet, 3H).

EXAMPLE 3 Deca-2,4,8-trienoic acid methyl ester

To a solution of 4-(diethoxy-phosphoryl)-but-2-enoic acid methyl ester(11.6 g, 49.2 mmol) in THF (70 ml) was added KOtBu (5.98 g, 49.2 mmol)at 0° C. The mixture was cooled to −78° C. and a solution of(Z)-hex-4-enal (4.00 g, 40.8 mmol) in THF (10 ml) was added dropwise.After the cooling bath was removed and the mixture had warmed up to roomtemperature, sat. NH₄Cl was added and the mixture was extracted withpentane. The organic phase was washed with water and brine, dried(MgSO₄) and concentrated in vacuo. The residue was distilled bulb tobulb (90° C./0.01 Torr) to yield (8Z, 2E)-deca-2,4,8-trienoic acidmethyl ester (2.4 g, 33%) as a 7/3 mixture of the (4E/Z)isomers.

¹H-NMR (200 MHz, CDCl₃): 7.69-7.20 (m, 1H), 6.29-5.31 (m, 5H), 3.76,3.74 (2s, 3H, OMe), 2.45-2.13 (m, 4H), 1.61 (d, J=6.5 Hz, 3H, 10H) ppm;MS (EI): 180 (M⁺, 2), 149 (6), 121 (10), 111 (27), 93 (28), 67 (51), 59(32), 55 (100), 39 (35), 29 (28). IR (neat): 3015m, 2949m, 1720s, 1644m,1435m, 1264s, 1137m cm⁻¹.

Deca-2,4,8-trienoic acid (2-hydroxy-2-methyl-propyl)-amide (Compound 2in the Table above)

Deca-2,4,8-trienoic acid methyl ester (1.90 g, 10.56 mmol) wassaponified with NaOH (2.11 g, 52.8 mmol) in H₂O/MeOH (5/1, 60 ml) during2d. The crude reaction mixture was acidified with HCl (2N) to pH=1 andextracted 5 times with MTBE. The organic phase was washed with brine,dried (MgSO₄) and concentrated in vacuo. The residue was dissolved inCH₂Cl₂ (30 ml) containing a drop of DMF and treated over night withoxalyl chloride (2.0 g, 15.7 mmol). The solvent was removed in vacuo(while keeping the temperature at ˜20° C.), the residue was redissolvedin CH₂Cl₂ (10 ml) and added to a solution of1-amino-2-methyl-propan-2-ol (1.1 g, 12.4 mmol) and triethyl amine (1.5g, 15 mmol) in CH₂Cl₂ (20 ml). The mixture was stirred for 5 h and wasthen quenched with water and extracted with CH₂Cl₂. The organic phasewas washed with 1N HCl, water and brine, dried (MgSO₄) and concentratedin vacuo. (2E,8Z)-Deca-2,4,8-trienoic acid(2-hydroxy-2-methyl-propyl)-amide (2.0 g, 80%) crystallized from ethylacetate/hexane as a 7/3 mixture of the (4E/Z)isomers in form of slightlyyellow crystals.

(4E)-Isomer: ¹HNMR (400 MHz, CDCl₃): 7.19 (dd, J=15.0 Hz, 10.3 Hz, 1H,3H), 6.56 (bt, J=6.0 Hz, 1H, NH), 6.19-6.03 (m, 2H, 4,5H), 5.86 (d,J=15.0 Hz, 1H, 2H), 5.52-5.44 (m, 1H), 5.39-5.32 (m, 1H), 3.49 (s, 1H,OH), 3.33 (d, J=6.0 Hz, 2H, NH—CH₂), 2.25-2.13 (m, 4H, 6,7-H), 1.60 (d,J=6.5 Hz, 3H, 10-H) ppm. MS (EI): 237 (M⁺, 4), 179 (62), 164 (13), 149(23) 124 (48), 110 (100), 94 (22), 84 (25), 66 (30), 59 (47), 55 (88),41 (24), 30 (34). IR (neat): 3287br(OH), 2974m, 2931m, 1658s, 1627s,1609s, 1537s, 1179m, 1161m, 996m, 913m cm⁻¹.

EXAMPLE 4

A flavour composition is formed of the following ingredients:

-   80 g Vegetable oil-   6.153 g Black pepper oil-   4.338 g alpha-phellandrene-   2.8575 g caryophyllene-   0.72 g ginger oil-   0.696 g compound 2-   0.1135 g 4-terpinenol-   0.0540 g linalool-   0.03 g cedar leaf oil-   0.018 g celery seed oil

The ingredients are thoroughly mixed before adding “Tween” (trade mark)surfactant 80 q. s. 100. Additional mixing is performed until a clear,pale to medium yellow liquid is obtained.

When this liquid is added to a soup at 0.2%, the above formula adds apleasurable pungency and tingling sensation to the soup.

1. A compound according to the formula (I)

or mixtures thereof wherein, R′ is H, or OH, and R″ is a phenyl radical;or phenyl substituted with C1-C4 alkyl or alkoxy; or a group

wherein m is 1, 2 or 3 R′″ and R″″ are independently selected from H,C1-C4 alkyl, benzyl, or R′″ and R″″ together with the carbon atom towhich they are attached form a 5- or 6-membered carbocyclic ring, R^(v)is alkyl or alkenyl or a substituted alkyl or unsubstituted alkenyl thatdoes not contain any aliphatic conjugated double bonds, and n is 1 or 2.2. A compound according to claim 1 wherein R′ is OH.
 3. A compoundaccording to claim 1 wherein n is
 1. 4. A compound according to claim 1selected from the group consisting of

Compound R′ R″ R′″ R″″ n Aromatic H A Methyl Methyl 1 Structure 2 H BMethyl Methyl 2 85-0344 OH C Methyl Methyl 2 85-0960 OH D Methyl Methyl2 85-2492 OH B Methyl Methyl 2 85-2493 H E Methyl Methyl 2

according to the foregoing table, wherein, in the be table A is phenyland B, C, D and E, are representative of the group

wherein in B Rv is an ethyl radical C Rv is a methyl radical, and D Rvis a cis-pent-2-enyl radical E Rv is an n-pentyl radical
 5. Use of acompound according to claim 1 as an ingredient in flavour compositions.6. A flavour composition according comprising a compound or mixture ofcompounds as defined in claim
 1. 7. A food product containing a compoundof formula (I) defined in claim 1 or mixtures thereof in amounts of0.001 to 10% by weight.
 8. A beverage product containing a compound offormula (I) defined in claim 1 or mixtures thereof in amounts of 0.0001to 500 mg/Kg.
 9. A personal care product or cosmetic product containinga compound of formula (I) defined in claim 1 or mixtures thereof inamounts of 0.01 to 10% by weight.